Background: Cigarette smoking is the most common cause of preventable morbidity and mortality in the US. Stress is a key component in the failure to quit. Data from our laboratory and others suggest that mindfulness training may be effective for the treatment of addictions by specifically targeting stress. Also, it has been suggested that we have an inherent capacity for mindfulness, but that the degree to which it is "naturally" used (i.e., trait-like) varies among individuals. This variability may affect one's ability to deal with stress and thus recover from addictions. No studies measuring the neural correlates of meditation in smokers have been reported. Assessment of pre-treatment regional brain activation patterns during two distinct mindfulness meditations may help to identify individual capacities for mindfulness, and how these patterns may relate to treatment outcomes. Evaluating how activation patterns during meditation change pre- to post-treatment may be useful in identifying key elements of mindfulness training and its effects on stress. Study Design: This proposal will add an fMRI paradigm to an ongoing randomized clinical trial of nicotine-dependent individuals in order to evaluate neural activity associated with meditation training before and after undergoing four weeks of mindfulness training or smoking cessation therapy (n = 20 in each group). Research Goals: The proposed fMRI study will address the following research questions. 1) Do defined brain activation patterns in nicotine-dependent individuals differ among two different, standardized meditation practices and the resting state before treatment? 2) What is the correlation between pre-treatment brain activity during each of these meditations and smoking cessation treatment outcomes? 3) Are there detectable changes in neural activation during meditation after mindfulness training versus after standard smoking cessation therapy (and do these changes correlate with treatment outcomes)? Anticipated Results: We anticipate that before treatment, nicotine-dependent individuals in both groups will show activation of midline structures associated with the default-mode network and that this activation will correlate with treatment outcomes. Additionally, the mindfulness training group will show decreased brain activation in these cortical areas during meditation (post- vs. pre-treatment) compared to the smoking cessation therapy group (post- vs. pre-treatment), and these changes will correlate with treatment outcomes. Benefit for Society: Expanding our current pilot work on the use of mindfulness training to augment smoking outcomes by including fMRI analysis will begin to delineate the functional mechanisms through which two standardized approaches to mindfulness meditation operate. Data concerning which of the two meditation techniques tested is most correlated within smoking cessation will also be generated. This will help advance our understanding of how mindfulness training affects the brain, what processes affect behavioral change, and how these can be applied to improve treatment of nicotine dependence and other addictions. PUBLIC HEALTH RELEVANCE: As an adjunct to an ongoing randomized clinical trial evaluating mindfulness training in outpatient smokers, the proposed study will use fMRI to address the following research questions: 1) Do defined brain activation patterns in nicotine-dependent individuals differ among two different, standardized meditation practices and the resting state before treatment? 2) What is the correlation between pre-treatment brain activity during each of these meditations and smoking cessation treatment outcomes? 3) Are there detectable changes in neural activation during meditation after mindfulness training versus after standard smoking cessation therapy (and do these changes correlate with treatment outcomes)?